The CON−H^…+NH₂ Blue-Shifting H-Bond Stabilizing Effect on Z Secondary Amides and Cyclic System Conformational Rearrangement through an Alkylamine-Chain Migration Pathway

Scheme 4

Conformational isomers 5-6 upon deprotonation regulated by two mechanisms and reference compounds 7-8. The carbamoyl oxygen atom initial protonation is efficient and increases the secondary amide stabilization energy in general; whereas, the nitrogen atom protonation has the capability for conformational change (∼) as a result of repulsive orbital-orbital interactions in the less stable tetrahedral intermediate (see steps in the migration course upon activation by water). The intramolecular rearrangement step occurs with retention of the stereochemistry at the migrating center under the reaction conditions.